Ewing's sarcoma is the second most common bone tumor in children and adolescents. When presenting with metastases or relapse, it is an often fatal disease. Unfortunately, little is known about the epidemiology or genetic risks for this deadly cancer. Ewing's sarcoma almost always contains a specific translocation between EWS-FLI1, are another fusion partner with the EWS gene. Recent laboratory investigations have revealed that a minimum number of microsatellite repeats are necessary in the promoter regions of the genes affected by the EWS-FLI1 translocation protein. These microsatellite repeats are necessary for Ewing's sarcoma tumors to develop in vitro. Another commonly reported feature of Ewing's sarcoma includes a very strong Caucasian predominance (the disease rarely occurs in Asian or African-American patients and only occasionally occurs in Hispanic patients) and also the association of increased hernias in patients who develop Ewing's sarcoma. For this study, we will collect DNA from 550 cases of Ewing's sarcoma in North America, along with DNA from both parents when available. We will then investigate: 1) whether children who develop Ewing's sarcoma have inherited longer microsatellite regions from their parents, 2) if non-Caucasian cases of Ewing's sarcoma actually contain genetic Caucasian ancestral markers, and 3) if cases of Ewing's sarcoma have inherited genomic variants associated with Ewing's sarcoma translocation genes and hernia-development. This study will help to explain the genetic risks for Ewing's sarcoma, one of the most deadly cancers in children and young adults. PUBLIC HEALTH RELEVANCE: Ewing's sarcoma is one of the most common and deadly bone tumors in children and young adults, but little is known about its genetic epidemiology. This study will explore the biological basis of risk for Ewing's sarcoma, including its ethnic predominance in Caucasians and association with hernias. A better understanding of the genetic risks for Ewing's sarcoma may lead to prevention strategies, better risk stratification, and even the identification of new therapeutic targets.